A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

A simple algorithm to predict non-compliance with organ at risk dose-volume constraints when planning intensity modulated post-prostatectomy radiation treatment: 'Why we should put the CART before the horse'.

INTRODUCTION: It is not always apparent when the optimal IMRT/VMAT plan for post-prostatectomy radiotherapy (PPRT) has been achieved. Individual variation in patient anatomy is a key contributor. This study aimed to create a model to determine the probability of rectum and/or bladder doses exceeding planning goals based on individual patient anatomy prior to planning. METHODS: The IMRT/VMAT PPRT plans from 200 men were randomly and evenly allocated into the Training Cohort and the Validation Cohort. Univariate and multivariate analysis of the Training Cohort identified variables which impacted bladder and rectal doses. Significant variables were included in a Classification and Regression Tree (CART) analysis. The resultant algorithm was then applied to the Validation Cohort. RESULTS: On multivariate analysis, prescription dose; bladder and rectal volume; lymph node treatment; and percentage of bladder and rectal overlap with the PTV were significant variables. Following CART analysis, the overlap volume (OV) for both rectum (rectum overlap > 20%) and bladder (bladder overlap > 20%) were the key drivers of meeting planning goals. Treatment of pelvic lymph nodes was included as the secondary driving factor for bladder (but not rectal) dose. On application to the Validation Cohort, CART analysis predicted 95% and 87% of patients who would meet bladder and rectal planning goals respectively. CONCLUSIONS: A simple algorithm was developed to predict plan quality by using the OV of the bladder and rectum with the PTV. This algorithm may be used a priori to assess the planning process in the context of variable anatomy, and to optimise planning quality and efficiency.